Circular Scale of Time as a Way of Calculating the Quantum-Mechanical Perturbation Energy Given by the Schrödinger Method in QM/MM rational drug discovery and molecular diversity for the construction of an anti-alpha-bungarotoxin binding MAP-p6.7 peptide mimetic ligand against nicotinic receptor binding site as a potent snake neurotoxin synthetic antidote.

The Schrödinger perturbation energy for an arbitrary order N of the perturbation has been presented with the aid of a circular scale of time. The method is of a recurrent character and developed for a non-degenerate quantum state. It allows one to reduce the inflation of terms necessary to calculate known from the Feynman’s diagrammatical approach to a number below that applied in the original Schrödinger perturbation theory. he structure of peptide p6.7, a mimotope of the nicotinic receptor ligand site that binds alpha-bungarotoxin and neutralizes its toxicity, was compared to that of the acetylcholine binding protein. The central loop of p6.7, when complexed with alpha-bungarotoxin, fits the structure of the acetylcholine binding protein (AChBP) ligand site, whereas peptide terminal residues seem to be less involved in toxin binding. The minimal binding sequence of p6.7 was confirmed experimentally by synthesis of progressively deleted peptides. Affinity maturation was then achieved by random addition of residues flanking the minimal binding sequence and by selection of new alpha-bungarotoxin binding peptides on the basis of their dissociation kinetic rate. The MAP peptide binds alpha-bungarotoxin in solution and inhibits its binding to the receptor with a K(A) and an IC(50) similar to the monomeric peptide. Peptidomimetics are designed to circumvent some of the problems associated with a natural peptide: e.g. stability against proteolysis (duration of activity) and poor bioavailability. In this regard, we discuss its potential to become a routinely used drug design tool of QM/MM in rational drug discovery and molecular diversity for the construction of anti-alpha-bungarotoxin binding peptide mimetic antidotes consisting of essential elements with high affinity and promised vivo efficiency. Finally, we applied to the Circular Scale of Time computations as a Way of Calculating the Quantum-Mechanical Perturbation Energy Given by the Schrödinger Method in QM/MM rational drug discovery and molecular diversity for the construction of an anti-alpha-bungarotoxin binding MAP-p6.7 peptide mimetic ligand against nicotinic receptor binding site as a potent snake neurotoxin synthetic antidote.

Grigoriadis Ioannis, Grigoriadis George, Grigoriadis Nikolaos, George Galazios (2017) Circular Scale of Time as a Way of Calculating the Quantum-Mechanical Perturbation Energy Given by the Schrödinger Method in QM/MM rational drug discovery and molecular diversity for the construction of an anti-alpha-bungarotoxin binding MAP-p6.7 peptide mimetic ligand against nicotinic receptor binding site as a potent snake neurotoxin synthetic antidote.